English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Previous studies have shown that hypoxic preconditioning attenuates prion-mediated neurotoxicity by upregulating hypoxia inducible factor-1α (HIF-1α). However, the mechanisms behind the HIF-1α-mediated neuroprotective effects in neurodegenerative disorders, including prion diseases, are unclear. It is well known that HIF-1α regulates Wnt/β-catenin signaling and that β-catenin protects neurons against misfolded protein-mediated disorders, including Alzheimer's and Parkinson's disease by preventing mitochondrial malfunction. Thus, we hypothesized that the mechanisms responsible for HIF-1α-mediated neuroprotection are associated with β-catenin activation induced by the regulation of mitochondrial function. We used the SH-SY5Y human neuroblastoma cell line and treated the cells with melatonin and then exposed them to the prion protein, PrP, or the β-catenin inhibitor, ICG-001. TUNEL assay was used to measure apoptosis. β-catenin expression measured by western blot analysis. The results revealed that HIF-1α prevented prion protein (PrP) (106-126)-induced neurotoxicity by activating β-catenin. Moreover, HIF-1α-induced β-catenin activation prevented the PrP (106-126)-induced mitochondrial damage under hypoxic conditions, as evidenced by the higher mitochondrial transmembrane potential values in the cells exposed to hypoxic conditions. These results indicate that the regulation of β-catenin activation by HIF-1α may be a therapeutic strategy for prion-mediated disorders.

HIF-1α-induced β-catenin activation prevents prion-mediated neurotoxicity